Barney Viengkhou

Key Points Interleukin-6 and interferon-alpha regulate key microglia functions in opposite ways. Exposure time of cytokine stimulation affects microglia responses. Interleukin-6 stimulates microglia migration and phagocytic capability. Interferon-alpha inhibits microglia migration and phagocytic capability. INTRODUCTION Microglia play essential roles during development, homeostasis and diseases of the central nervous system (CNS), as reviewed by West et al. and Borst et al. [1, 2].

Highlights • Neurotoxic IFN-α in Aicardi-Goutières syndrome (AGS) is primarily of cerebral origin • Endothelial cells are critical cellular targets of neurotoxic IFN-α • Chronically elevated intracerebral IFN-α causes a distinct cerebral microangiopathy • Neurodegeneration arises as a secondary consequence of IFN-α-driven microangiopathy Summary Aicardi-Goutières syndrome (AGS) is an autoinflammatory disease characterized by aberrant interferon (IFN)-α production.

Abstract Chronic and elevated levels of the antiviral cytokine IFN-α in the brain are neurotoxic. This is best observed in patients with genetic cerebral interferonopathies such as Aicardi-Goutières syndrome. Cerebral interferonopathies typically manifest in early childhood and lead to debilitating disease and premature death. There is no cure for these diseases with existing treatments largely aimed at managing symptoms. Thus, an effective therapeutic strategy is urgently needed.